15-73951937-C-G

Position:

• chr15-73951937-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.*100C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,155,798 control chromosomes in the GnomAD database, including 347,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38791 hom., cov: 33)
  • Exomes 𝑓: 0.78 (308639 hom.)
• Consequence: LOXL1 NM_005576.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.*100C>G		3_prime_UTR_variant	7/7	ENST00000261921.8
LOXL1	XM_017022179.2	c.*100C>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.*100C>G		3_prime_UTR_variant	7/7	1	NM_005576.4	P1
LOXL1	ENST00000562548.1	n.910C>G		non_coding_transcript_exon_variant	3/3	2
LOXL1	ENST00000567675.1	n.261C>G		non_coding_transcript_exon_variant	3/3	3
LOXL1	ENST00000566011.5			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106660 AN: 152062 Hom.: 38761 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.693

GnomAD4 exome AF: 0.782 AC: 784402 AN: 1003620 Hom.: 308639 Cov.: 13 AF XY: 0.779 AC XY: 381062 AN XY: 489078

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.726

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.701 AC: 106738 AN: 152178 Hom.: 38791 Cov.: 33 AF XY: 0.701 AC XY: 52152 AN XY: 74412

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.694

Alfa AF: 0.741 Hom.: 5298

Bravo AF: 0.693

Asia WGS AF: 0.592 AC: 2057 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8818; hg19: chr15-74244278;